Preparations of human leukocyte (alpha) and fibroblast (beta) interferon were given intramuscularly to rabbits and monkeys, and circulating interferon was measured. In rabbits, but not in monkeys, a marked difference between the two interferons was noted in that higher titers of circulating antiviral activity were obtained with leukocyte than with fibroblast interferon. In mice, injected interperitoneally, a similar difference could be noted. However, levels of antiviral activity in homogenates of spleens and lungs did not differ between mice injected with either interferon. Fibroblast interferon that was injected intrathecally in monkeys was found to diffuse throughout the cerebrospinal canal and to reach the serum compartment. Some interferon could also be recovered from the pia mater surrounding the brain hemispheres, but none was found in the deeper layers of the brain.